Information processing speed was assessed using the visual threshold serial addition test (VT-SAT), a computerized modification of the PASAT designed to assess processing speed by controlling for performance accuracy. Persons with MS (N=43) and healthy individuals (N=32) were administered the VT-SAT varying working memory loads (1-back versus 2-back). Results indicated that at the lower working memory load (1-back) all individuals with MS were able to achieve a working memory performance level equivalent to healthy individuals, but required significantly more processing time to do so. In contrast, at the higher working memory load (2-back), about 70% of MS participants were able to achieve a performance level equivalent to healthy individuals, but again required significantly more processing time. The results are discussed in the context of the dynamic nature of the relationship between processing speed and working memory performance, emphasizing the dependence of this relationship on other cognitive and disease-related factors.

Objective examination of cognitive fatigue in persons with multiple sclerosis (MS). Participants: Fifty-six individuals with MS and 39 age-and education-matched healthy control subjects. Main Outcome Measures: Cognitive fatigue, operationalized as the failure to sustain effort over the course of a continuous working memory task; performance on the Paced Auditory Serial Addition Test was examined, with number of correct responses generated and responses produced under conditions of sustained central executive load as the dependent variables. Results: Cognitively impaired MS subjects produced significantly fewer correct responses than either nonimpaired MS subjects or healthy control subjects, who performed at a comparable level. Both MS groups, however, showed susceptibility to cognitive fatigue significantly earlier in time than the healthy group. Conclusions: Fatigue can influence performance even in the absence of cognitive impairment.

To examine the clinical utility of the Letter-Number Sequencing (LNS) subtest of the Wechsler Adult Intelligence Scale-III and the Paced Auditory Serial Addition Test (PASAT) to detect cognitive decline in persons with multiple sclerosis (MS). Design: Case-control study. Setting: Outpatient rehabilitation research institution. Participants: Fifty-two adults with clinically definite MS. Main Outcome Measures: LNS standard score and number correct on the PASAT. Results:The PASAT was more sensitive to information processing deficits in persons with MS than was the LNS, perhaps due to a significant processing speed component in the former. Conclusions: The PASAT and the LNS have differential clinical utility, inasmuch as the PASAT assesses not only working memory ability but processing speed as well.

In humans, anterograde amnesia can result from damage to the medial temporal (MT) lobes (including hippocampus), as well as to other brain areas such as basal forebrain. Results from animal classical conditioning studies suggest that there may be qualitative differences in the memory impairment following MT vs. basal forebrain damage. Specifically, delay eyeblink conditioning is spared after MT damage in animals and humans, but impaired in animals with basal forebrain damage. Recently, we have likewise shown delay eyeblink conditioning impairment in humans with amnesia following anterior communicating artery (ACoA) aneurysm rupture, which damages the basal forebrain. Another associative learning task, a computer-based concurrent visual discrimination, also appears to be spared in MT amnesia while ACoA amnesics are slower to learn the discriminations. Conversely, animal and computational models suggest that, even though MT amnesics may learn quickly, they may learn qualitatively differently from controls, and these differences may result in impaired transfer when familiar information is presented in novel combinations. Our initial data suggests such a two-phase learning and transfer task may provide a double dissociation between MT amnesics (spared initial learning but impaired transfer) and ACoA amnesics (slow initial learning but spared transfer). Together, these emerging data suggest that there are subtle but dissociable differences in the amnesic syndrome following damage to the MT lobes vs. basal forebrain, and that these differences may be most visible in non-declarative tasks such as eyeblink classical conditioning and simple associative learning.

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